Microarray Approach Reveals the Relevance of Interferon Signaling Pathways with Rat Liver Restoration Post 2/3 Hepatectomy at Cellular Level

Abstract

The immunomodulator interferons are assumed not only to fight tumor progress but also to inhibit liver regeneration by inactivating Kupffer cells. The potential mechanism is still poorly characterized. In particular, the relevance of interferon signaling to liver regeneration at cellular level still remains unknown. In this study, 8 types of rat liver cells from the regenerating liver at 10 recovery time points were separately isolated by percoll density gradient centrifugation and immunomagnetic bead. Transcription profiles of interferon-signaling pathway genes in each cell type along the time course of liver restoration were detected using Rat Genome 230 2.0 Array covering about 12,727 known genes. The chip data demonstrated that hepatocyte mainly up-regulated the IFN-alpha1-mediated JAK/STAT pathway genes; biliary epithelial cell mostly expressed the IFN-beta1-mediated p38 MAPK pathway genes; while the IFN-gamma-activated JAK/STAT pathway genes were down-regulated particularly in HSC, KC, and DC during liver regeneration. It is inferred that STAT3, in contrast to STAT1, seemingly takes a more active role in IFN-alpha1-mediated JAK/STAT pathway in hepatocyte; IFN-beta1-mediated p38 MAPK pathway possibly to some extent affects inflammation and apoptosis of biliary epithelial cell during liver regeneration; IFN-gamma-induced JAK/STAT pathway may be associated with the attenuated apoptosis induction in HSC, KC, and DC. Our data suggested that a better understanding about how interferon signals at liver cell level might be helpful in developing an effective approach to protecting against the inhibition of regeneration.